Matthew R. Smith, M.D., from Massachusetts General Hospital Cancer Center in Boston, and colleagues assessed the effects of denosumab on the prevention of bone metastasis or death in men with non-metastatic castration-resistant prostate cancer, at high risk of bone metastasis. A total of 1,432 participants were randomly allocated in a 1:1 ratio to receive subcutaneous denosumab 120 mg or subcutaneous placebo every four weeks. Bone-metastasis-free survival, determined by time to first occurrence of bone metastasis, or any-cause death was the primary end point.

The investigators found that, compared to the placebo group, bone-metastasis-free survival was significantly increased in the denosumab group (29.5 versus 25.2 months; hazard ratio [HR], 0.85). The time to first bone metastasis was significantly delayed in the denosumab group (33.2 versus 29.5 months; HR, 0.84). The two groups did not differ in terms of overall survival (P = 0.91). Similar rates of adverse and serious adverse events were seen in both groups, except for osteonecrosis of the jaw and hypocalcemia, which occurred in more patients treated with denosumab than placebo.

"Our finding that denosumab increases bone-metastasis-free survival provides clinical evidence for the important role of the bone microenvironment and RANKL signaling in development of bone metastases in men with prostate cancer," the authors write.

Several authors disclosed financial relationships with pharmaceutical companies, including Amgen Inc., which funded the study and manufactures denosumab.